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P C Anderson

Publications and source records attributed to P C Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1995

Crystal structures of HIV-2 protease in complex with inhibitors containing the hydroxyethylamine dipeptide isostere.

BACKGROUND: The HIV protease is essential for the life cycle of the virus and is an important target for the development of therapeutic treatments against AIDS. The structures of HIV protease in complex with different inhibitors have helped in understanding the interactions between inhibitors and the protease and in the design and optimization of HIV protease inhibitors. RESULTS: We report here crystal structures at up to 1.7 A resolution of the homodimeric HIV-2 protease in complex with seven inhibitors containing the hydroxyethylamine dipeptide isostere. A novel dimethylphenoxyacetyl group that is present in some of these inhibitors is inserted between residues 48' and 49' in the flap of the protease and residues 29' and 30' (where a prime indicates a residue in the second monomer), which undergo a conformational change to accommodate the phenyl ring of the inhibitor. CONCLUSIONS: This study shows that besides the residues in the flap and residues 79-81 in the S1 substrate-binding pocket which undergo conformational changes upon inhibitor binding, residues 29 and 30 can also adapt their conformation to fit certain inhibitors. Conformational flexibility of the HIV protease plays an important role in inhibitor binding.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Determination of kinetic rate constants for the binding of inhibitors to HIV-1 protease and for the association and dissociation of active homodimer.

Association and dissociation rate constants for a competitive inhibitor of HIV-1 protease were determined by a novel method employing a pair of integrated rate equations. This method, termed the paired progress curve method, is both rapid and reproducible. Progress curves, taken at a single concentration of inhibitor, are analyzed simultaneously to determine association and dissociation rate constants, the concentration of active sites, and the catalytic rate constant. The method is applied to BILA 398, a compound for which the cocrystal structure with HIV-2 protease has been reported recently [Tong, L., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8387-8391]. This compound exhibited an association constant of 1.6 x 10(7) M-1 s-1 and a dissociation constant of 1.0 x 10(-4) s-1 corresponding to a binding affinity constant of 6.4 x 10(-12) M. During the course of the analysis, nonlinearity was observed in control reactions containing enzyme and substrate only. This was subsequently shown to be due to a reversible inactivation process resulting from enzyme dilution. Integrated rate equations were developed on the basis of the dissociation of active dimeric enzyme during dilution and a reassociation of dilute monomers following the addition of substrate. The equations were modeled to the data, yielding a dissociation constant of 1.9 x 10(-3) s-1 and an association constant of 9.2 x 10(5) M-1 s-1 for the monomer-dimer interconversion process. This corresponds to an equilibrium constant of 4 x 10(-9) M for the dimerization of HIV-1 protease.

Binding, Competitive↗
PubMed1994

Production of fertile transgenic maize by electroporation of suspension culture cells.

Fertile, transgenic maize plants were generated by electroporation of suspension culture cells that were treated with a pectin-degrading enzyme. Electroporation of cells from two different suspension cultures, one derived from A188 X B73 and one derived from a B73-related inbred, with a plasmid containing the bar gene, resulted in high-frequency recovery of stably transformed callus lines. Plants were regenerated from thirteen transformed callus lines and transmission of bar to progeny was demonstrated.

Blotting, Southern↗
PubMed1994

Snake bites.

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Animals↗
PubMed1993

Crystal structure of human immunodeficiency virus (HIV) type 2 protease in complex with a reduced amide inhibitor and comparison with HIV-1 protease structures.

The crystal structure of HIV-2 protease in complex with a reduced amide inhibitor [BI-LA-398; Phe-Val-Phe-psi (CH2NH)-Leu-Glu-Ile-amide] has been determined at 2.2-A resolution and refined to a crystallographic R factor of 17.6%. The rms deviation from ideality in bond lengths is 0.018 A and in bond angles is 2.8 degrees. The largest structural differences between HIV-1 and HIV-2 proteases are located at residues 15-20, 34-40, and 65-73, away from the flap region and the substrate binding sites. The rms distance between equivalent C alpha atoms of HIV-1 and HIV-2 protease structures excluding these residues is 0.5 A. The shapes of the S1 and S2 pockets in the presence of this inhibitor are essentially unperturbed by the amino acid differences between HIV-1 and HIV-2 proteases. The interaction of the inhibitor with HIV-2 protease is similar to that observed in HIV-1 protease structures. The unprotected N terminus of the inhibitor interacts with the side chains of Asp-29 and Asp-30. The glutamate side chain of the inhibitor forms hydrogen bonds with the main-chain amido groups of residues 129 and 130.

Amino Acid Sequence↗
PubMed1992

Lichen planus.

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Humans↗
PubMed1991

Loxoscelism threatening pregnancy: five cases.

Envenomation by the spider Loxosceles reclusa in five pregnant women proved to have no sustained adverse effects on mother or baby when managed conservatively only with low-dose prednisone. A striking toxic erythema of the skin, common with the bite of the spider, caused the greatest discomfort and concern for the patients but proved to be entirely tractable. No episodes of hemolysis, disorders of coagulation, or renal damage were discovered. There is no clinical evidence of any special risk during pregnancy in the event of loxoscelism.

Adult↗
PubMed1991

Morphology of peritoneal dialysis catheter tunnel: macroscopy and light microscopy.

There is scanty knowledge of the morphology of peritoneal dialysis catheter tunnels in humans, even though such knowledge may impact on peritoneal catheter design, implantation and postimplantation care. Past descriptions of catheter tunnels are based mainly on data from animal experiments. Based on these data, it has been assumed that epidermal spreading is inhibited by collagen fibers ingrown into the cuff. Our preliminary investigation indicated that this may not be the case in humans and led us to study catheter tunnel morphology in more detail. Eighteen catheter tunnels (2-5mm of tissue around the catheters) were removed in 17 peritoneal dialysis patients. The catheters were inserted 30 to 2013 days prior to removal (median 366 days). The catheters were removed electively or because of infectious or noninfectious complications. Contrary to the observations in animals, in only 1 case did epithelium extend to the cuff with only a minimal amount of granulation tissue present at the end of a 9 mm long sinus tract. In the remaining cases, the leading edge of the epithelium always met granulation tissue 1-14 mm from the exit, and the cuffs were found 8-33 mm from the exit. In tunnels older than 197 days, dense fibrous tissue was ingrown into the cuffs, and a dense fibrous capsule surrounded the cuff. The uninfected intercuff segment formed a pseudosheath, indistinguishable from a tendon sheath or synovial membrane. Infection in the catheter tunnel propagates through the part of the cuff adjacent to the tubing inside the capsule, suggesting that the cuff per se does not constitute a major barrier for spreading infection. This observation, by exclusion, infers that the beneficial role of an external cuff in decreasing exit infections is by providing firm anchorage of the catheter resulting in restriction of its piston like movement and thereby minimizing trauma and inward conveyance of outer sinus tract flora.

Adolescent↗
PubMed1990

Circinate plaques heralding juvenile chronic myelogenous leukemia.

Plaques of leukemia cutis were the first manifestation of juvenile chronic myelogenous leukemia in a 2-year-old. This is a rare and usually fatal form of childhood leukemia. Only three cases of leukemia cutis associated with juvenile chronic myelogenous leukemia have been published.

Child, Preschool↗